Letter

In an observational study in a recent issue of Critical Care, we demonstrated that platelet function, as assessed by impedance aggregometry, is
reduced in patients with severe sepsis and poor prognosis [1]. In the present study, we investigated whether the prototypic endotoxin lipopolysaccharide
(LPS) (Escherichia coli; serotype 0.111:B4; Sigma-Aldrich, Munich, Germany) exerts comparable effects in
an in vitro model. Therefore, heparinized blood samples were drawn from the antecubital vein of
healthy probands. After incubation of samples with LPSs (100 μg/mL) or vehicle for
240 minutes at 37°C, samples were subjected to impedance aggregometry (Roche Diagnostics
Deutschland GmbH, Mannheim, Germany), and aggregation was induced by adenosine diphosphate
(ADP), collagen, thrombin receptor-activating peptide (TRAP), or arachidonic acid.

Incubation of whole blood samples with LPS markedly inhibited platelet function as
revealed by determination of the impedance aggregometry variable of area under curve
(expressed in arbitrary units). In LPS-treated samples, platelet function was significantly
reduced in comparison with vehicle-treated samples when collagen (−55%, P = 0.008), ADP (−45%, P = 0.008), or TRAP (−20%, P = 0.04) served as the activator. In contrast, no LPS-induced decrease in platelet
function was detectable when arachidonic acid was used as the activator (Figure 1).

Our in vitro findings on LPS-induced inhibition of platelet aggregation closely agree with our
recent observational study in patients with severe sepsis. In both studies, the decrease
in platelet function was dependent on the activator used and the ranking of activators
was identical (collagen > TRAP > ADP). Moreover, our finding that LPS did not reduce
arachidonic acid-induced platelet aggregation is in agreement with our previous observational
study. In contrast to the other activators, arachidonic acid was neither an independent
predictor of the diagnosis of severe sepsis nor an independent predictor of the outcome
in severe sepsis.

Thus, the present study demonstrates that the decrease in platelet aggregation seen
in patients with severe sepsis can be mimicked in the in vitro setting, suggesting comparable pathophysiological mechanisms.